Chronic Venous Insufficiency (CVI) is characterized by chronic venous hypertension from blood pooling in the lower limbs [1, 2]. In healthy veins, muscle contractions efficiently pump blood back to the heart while venous valves close to prevent reflux [3]. Venous hypertension and CVI can develop in the presence of venous reflux, venous obstruction, and calf muscle pump dysfunction [1]. The resulting symptoms include leg pain, varicose veins, fatigue, venous edema, skin pigmentation, inflammation, induration, and ulceration [4]. The risk of developing CVI increases with age, body mass index, height, family history of CVI, European ancestry, Hispanic ethnicity, pregnancy, prolonged standing, straining during bowel movements, being female, and residing in an industrialized country [5-10].
Treatments for CVI include exercise, compression, medication, vein disabling, venous stenting, surgical correction, and valve replacement. Thus far these treatments have demonstrated varying levels of efficacy in reducing the symptom severity. In practice the most conservative treatment is applied first, typically compression stockings, with more invasive procedures being pursued when symptoms do not significantly improve [30]. The appropriateness of each treatment is further determined by the functionality of the calf muscle pump as well as the presence and location of venous reflux and obstruction [31]. The time spent by an individual caring for an ulcer has been found to be highly correlated with feelings of resentment and anger [11]. Therefore, in addition to symptom relief, the time required of an individual for a given treatment must be considered when evaluating its efficacy.
A prosthetic venous valve has the potential to correct reflux in the deep, superficial, and perforating venous systems. While alternative minimally invasive treatments have the potential to stop reflux in the superficial and perforating venous systems, currently only invasive treatments exist for the correction of deep venous reflux.
Dotter was the first to suggest the concept of a transcatheter venous valve [35]. Such a valve would meet the need for a minimally invasive treatment for deep venous reflux. Three types of replacement valves have been developed by various researchers: mechanical, bioprosthetic, and polymer. For the polymeric replacement valves, Moriyama developed two prosthetic valves made by electrospinning polyurethane fibers onto a stent [63]; Sathe designed a naturally closed prosthetic venous valve composed of Poly(vinyl-alcohol) (PVA) cryogel [62, 64-66]; and Midha developed a naturally open prosthetic venous valve with a lemon shaped orifice made with PVA [66].
While a transcatheter prosthetic venous valve has the potential of being an effective minimally invasive solution to venous reflux, particularly in the deep venous system, an adequate valve has yet to be developed. While venous reflux and outflow obstruction are major contributors to the development of CVI, none of the existing valves have been demonstrated to reduce reflux below that seen in individuals with venous reflux while also not increasing outflow resistance to venous obstruction levels. Of the few valves which have been tested in humans, only one has reported to have remained both patent and competent inside an individual for more than a year, but this valve was deemed unfit to further use for venous implantation [40]. Regarding the recent development of the Midha valve, it was suggested that thrombus had formed in response to elevated shear rates induced by radial buckling of the valves; the base of the valve had a propensity to radially buckle because of the ovular shape of the shoulder; and there is a tendency of the valve's leaflets to prolapse under retrograde pressure. Thus far prosthetic valves tested in animals or humans have commonly reported concerns with: thrombogenicity; biocompatibility; correct sizing, and subsequent fixation and functionality of the valve.
There is a need to develop a novel transcatheter prosthetic venous valve that has low thrombogenicity, is biocompatible, is sized correctly, is sufficiently competent, does not significantly obstruct forward flow, and can function in a distensible vein.